A major goal of the program project is to determine osteocyte function in response to mechanical loading. In[unreadable] order to accomplish this goal it will be necessary to relate osteocyte deformation and/or strain in bone tissue[unreadable] to the expression and function of different molecules expressed by osteocytes in response to mechanical[unreadable] loading. The overall support aim of this research core laboratory is to provide the mechanical loading[unreadable] instrumentation and define the loading protocols that will be applied in-vitro and in-vivo throughout the[unreadable] program project. Well-defined in-vitro, ex-vivo and in-vivo mechanical loading systems are of paramount[unreadable] importance in conducting the work proposed in the individual projects. Although the precise nature of the[unreadable] mechanical environment of osteocytes in-vivo is not known, the protocols described herein are generally[unreadable] accepted in the scientific community. This core will provide support to conduct in-vivo and in-vitro loading of[unreadable] bones and bone cells, as well as the capability to image cells in-vitro and ex-vivo during application of[unreadable] mechanical stimuli enabling the quantification of individual cell deformations. In addition, this core will be a[unreadable] research core where important questions regarding cell deformation in response to mechanical stimulation[unreadable] will be investigated. Understanding the physical deformation of osteocytes due to different mechanical[unreadable] stimulation will provide needed insight into differences observed in cell response. Our preliminary data[unreadable] suggest that the hypothesis that bone cells do not respond to bone matrix strain may be incorrect. We have[unreadable] shown that local peri-lacunar bone matrix strain can be up to 20,000 microstrain, an order of magnitude[unreadable] greater than in-vivo bone surface strains measured using a strain gage and on average is 4,000-7,000[unreadable] microstrain when macroscopic strains of 2,000 microstrain are applied to bone. We have shown that in-vitro[unreadable] osteocyte cell deformation due to this level of shear stress can be between approximately 5,000 and 50,000[unreadable] microstrain with a concomitant biological response measured such as an increase in PGE2 production. The[unreadable] research goals of this core are to quantify osteocyte deformation in-vitro resulting from both fluid flow[unreadable] generated shear stress and substrate stretching. Furthermore, to extend our current research findings, we[unreadable] will measure osteocyte deformation ex vivo in mice long bones due to globally applied structural bending[unreadable] loads. We will also begin to characterize the osteocyte microenvironment, which is integral in transmitting[unreadable] global structural loads and deformations to the osteocyte, by atomic force microscopy, nanoindentation, and[unreadable] Direct Raman imaging.